Genetic Association Studies: An Information Content Perspective

The availability of high-density single nucleotide polymorphisms (SNPs) data has made the human genetic association studies possible to identify common and rare variants underlying complex diseases in a genome-wide scale. A handful of novel genetic variants have been identified, which gives much hope and prospects for the future of genetic association studies. In this process, statistical and computational methods play key roles, among which information-based association tests have gained large popularity. This paper is intended to give a comprehensive review of the current literature in genetic association analysis casted in the framework of information theory. We focus our review on the following topics: (1) information theoretic approaches in genetic linkage and association studies; (2) entropy-based strategies for optimal SNP subset selection; and (3) the usage of theoretic information criteria in gene clustering and gene regulatory network construction.     

Justice and Medical Research: A Global Perspective

Economic globalization has profound implications for health. The scale of injustice at a global level, reflected in inexorably widening disparities in wealth and health, also has critical implications for health related research – in particular when the opportunities for exploiting research subjects are carefully considered. The challenge of developing universal guidelines for international clinical research is addressed against the background of a polarizing, yet interdependent, world in which all are ultimately threatened by lack of social justice. It is proposed that in such a world there is a need for new ways of thinking about research and its relevance to health at a global level. Responsibility to use knowledge and power wisely requires more radical changes to guidelines for research ethics than are currently under consideration.     

Census Parcels Cropping System Classification from Multitemporal Remote Imagery: A Proposed Universal Methodology

A procedure named CROPCLASS was developed to semi-automate census parcel crop assessment in any agricultural area using multitemporal remote images. For each area, CROPCLASS consists of a) a definition of census parcels through vector files in all of the images; b) the extraction of spectral bands (SB) and key vegetation index (VI) average values for each parcel and image; c) the conformation of a matrix data (MD) of the extracted information; d) the classification of MD decision trees (DT) and Structured Query Language (SQL) crop predictive model definition also based on preliminary land-use ground-truth work in a reduced number of parcels; and e) the implementation of predictive models to classify unidentified parcels land uses. The software named CROPCLASS-2.0 was developed to semi-automatically perform the described procedure in an economically feasible manner. The CROPCLASS methodology was validated using seven GeoEye-1 satellite images that were taken over the LaVentilla area (Southern Spain) from April to October 2010 at 3- to 4-week intervals. The studied region was visited every 3 weeks, identifying 12 crops and others land uses in 311 parcels. The DT training models for each cropping system were assessed at a 95% to 100% overall accuracy (OA) for each crop within its corresponding cropping systems. The DT training models that were used to directly identify the individual crops were assessed with 80.7% OA, with a user accuracy of approximately 80% or higher for most crops. Generally, the DT model accuracy was similar using the seven images that were taken at approximately one-month intervals or a set of three images that were taken during early spring, summer and autumn, or set of two images that were taken at about 2 to 3 months interval. The classification of the unidentified parcels for the individual crops was achieved with an OA of 79.5%.     

A Global Perspective on Trends in Nature-Based Tourism

Reports of rapid growth in nature-based tourism and recreation add significant weight to the economic case for biodiversity conservation but seem to contradict widely voiced concerns that people are becoming increasingly isolated from nature. This apparent paradox has been highlighted by a recent study showing that on a per capita basis, visits to natural areas in the United States and Japan have declined over the last two decades. These results have been cited as evidence of “a fundamental and pervasive shift away from nature-based recreation”—but how widespread is this phenomenon? We address this question by looking at temporal trends in visitor numbers at 280 protected areas (PAs) from 20 countries. This more geographically representative dataset shows that while PA visitation (whether measured as total or per capita visit numbers) is indeed declining in the United States and Japan, it is generally increasing elsewhere. Total visit numbers are growing in 15 of the 20 countries for which we could get data, with the median national rate of change unrelated to the national rate of population growth but negatively associated with wealth. Reasons for this reversal of growth in the richest countries are difficult to pin down with existing data, but the pattern is mirrored by trends in international tourist arrivals as a whole and so may not necessarily be caused by disaffection with nature. Irrespective of the explanation, it is clear that despite important downturns in some countries, nature-related tourism is far from declining everywhere, and may still have considerable potential both to generate funds for conservation and to shape people''s attitudes to the environment.     

Fecal Contamination of Drinking-Water in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Background

Access to safe drinking-water is a fundamental requirement for good health and is also a human right. Global access to safe drinking-water is monitored by WHO and UNICEF using as an indicator “use of an improved source,” which does not account for water quality measurements. Our objectives were to determine whether water from “improved” sources is less likely to contain fecal contamination than “unimproved” sources and to assess the extent to which contamination varies by source type and setting.

Methods and Findings

Studies in Chinese, English, French, Portuguese, and Spanish were identified from online databases, including PubMed and Web of Science, and grey literature. Studies in low- and middle-income countries published between 1990 and August 2013 that assessed drinking-water for the presence of Escherichia coli or thermotolerant coliforms (TTC) were included provided they associated results with a particular source type. In total 319 studies were included, reporting on 96,737 water samples. The odds of contamination within a given study were considerably lower for “improved” sources than “unimproved” sources (odds ratio [OR] = 0.15 [0.10–0.21], I² = 80.3% [72.9–85.6]). However over a quarter of samples from improved sources contained fecal contamination in 38% of 191 studies. Water sources in low-income countries (OR = 2.37 [1.52–3.71]; p<0.001) and rural areas (OR = 2.37 [1.47–3.81] p<0.001) were more likely to be contaminated. Studies rarely reported stored water quality or sanitary risks and few achieved robust random selection. Safety may be overestimated due to infrequent water sampling and deterioration in quality prior to consumption.

Conclusion

Access to an “improved source” provides a measure of sanitary protection but does not ensure water is free of fecal contamination nor is it consistent between source types or settings. International estimates therefore greatly overstate use of safe drinking-water and do not fully reflect disparities in access. An enhanced monitoring strategy would combine indicators of sanitary protection with measures of water quality. Please see later in the article for the Editors'' Summary     

Global Spatio-Temporal Patterns in Human Migration: A Complex Network Perspective

Migration is a powerful adaptive strategy for humans to navigate hardship and pursue a better quality of life. As a universal vehicle facilitating exchanges of ideas, culture, money and goods, international migration is a major contributor to globalization. Consisting of countries linked by multiple connections of human movements, global migration constitutes a network. Despite the important role of human migration in connecting various communities in different parts of the world, the topology and behavior of the international migration network and its changes through time remain poorly understood. Here we show that the global human migration network became more interconnected during the latter half of the twentieth century and that migrant destination choice partly reflects colonial and postcolonial histories, language, religion, and distances. From 1960 to 2000 we found a steady increase in network transitivity (i.e. connectivity between nodes connected to the same node), a decrease in average path length and an upward shift in degree distribution, all of which strengthened the ‘small-world’ behavior of the migration network. Furthermore, we found that distinct groups of countries preferentially interact to form migration communities based largely on historical, cultural and economic factors.     

Personalized Evaluation of Biomarker Value: A Cost-Benefit Perspective

For a patient who is facing a treatment decision, the added value of information provided by a biomarker depends on the individual patient’s expected response to treatment with and without the biomarker, as well as his/her tolerance of disease and treatment harm. However, individualized estimators of the value of a biomarker are lacking. We propose a new graphical tool named the subject-specific expected benefit curve for quantifying the personalized value of a biomarker in aiding a treatment decision. We develop semiparametric estimators for two general settings: (i) when biomarker data are available from a randomized trial; and (ii) when biomarker data are available from a cohort or a cross-sectional study, together with external information about a multiplicative treatment effect. We also develop adaptive bootstrap confidence intervals for consistent inference in the presence of nonregularity. The proposed method is used to evaluate the individualized value of the serum creatinine marker in informing treatment decisions for the prevention of renal artery stenosis.     

Managing Global Atmospheric Change: A U.S. Policy Perspective

There are several air pollution issues that concern the international community at the regional and global level, including acid deposition, heavy metals, persistent organic pollutants, stratospheric ozone depletion, and climate change. Governments at the regional and global levels have entered into various agreements in an effort to deal with these problems. This paper deals with two major global atmospheric change issues: stratospheric ozone depletion and climate change. The focus is on the policy responses of the United States to these global issues. The United States has signed and ratified international agreements to deal with both problems. The Vienna Convention and the Montreal Protocol on Substances that Deplete the Ozone Layer have led to an effort in both developed and developing countries to phase out ozone depleting substances. The United Nations Framework Convention on Climate Change (UNFCCC) has been signed and ratified by over 180 countries. The UNFCC contained no binding targets and timetables for emissions reductions. The Kyoto Protocol (1997) to the UNFCCC did contain targets and timetables for reductions of greenhouse gases on the part of developed countries. The United States has signed but not ratified the Kyoto Protocol. The United States has experienced some movement to reduce greenhouse gas emissions on the part of various levels of government as well as the private sector. The policy process is constantly informed by scientific research. In the case of stratospheric ozone depletion and climate change, much of this work is carried out under the auspices of international scientific panels. From a policy perspective, there is a great deal of interest in the use of indicators for assessing the scope and magnitude of these problems, both for fashioning policy responses as well as assessing the impact of adopted programs to reduce ozone depleting substances, and potentially, greenhouse gases. This paper will discuss some of the indicators used for stratospheric ozone depletion and climate change.     

Patterns of Annual Seed Production by Northern Hemisphere Trees: A Global Perspective

We tested whether annual seed production (masting or mast fruiting) in Northern Hemisphere trees is an evolved strategy or a consequence of resource tracking by comparing masting patterns with those of annual rainfall and mean summer temperatures, two environmental variables likely to correlate with available resources. There were generally significant negative autocorrelations between the seed crop in year x and year x+1 (year x+2 in species of Quercus requiring 2 yr to mature acorns), as expected if resources are depleted in mast years in part by switching resources from growth to reproduction. Spatial autocorrelation in annual seed production generally declined with distance but was statistically significant over large geographic areas. Variability in annual seed production was relatively high and inversely correlated with latitude and generally not bimodally distributed. Patterns of spatial autocorrelation in annual rainfall and summer temperatures are generally similar to those exhibited by annual seed production, and relative variability in annual rainfall is also inversely correlated with latitude. However, these environmental variables exhibit distinctly different patterns of temporal autocorrelation, are much less variable, and are more normally distributed than annual seed production. Combined with the inverse relationship between growth and reproduction previously documented, these results support the hypothesis that variability in annual seed production is an evolved strategy and that annual seed production is more or less normally distributed rather than an all-or-none phenomenon.     

Between Artifacts and Texts: Historical Archaeology in Global Perspective

Between Artifacts and Texts: Historical Archaeology in Global Perspective. Anders Andrén. Translated by Alan Crozier. New York: Plenum, 1998. 216 pp.     

Phytochromes: An Atomic Perspective on Photoactivation and Signaling

The superfamily of phytochrome (Phy) photoreceptors regulates a wide array of light responses in plants and microorganisms through their unique ability to reversibly switch between stable dark-adapted and photoactivated end states. Whereas the downstream signaling cascades and biological consequences have been described, the initial events that underpin photochemistry of the coupled bilin chromophore and the ensuing conformational changes needed to propagate the light signal are only now being understood. Especially informative has been the rapidly expanding collection of 3D models developed by x-ray crystallographic, NMR, and single-particle electron microscopic methods from a remarkably diverse array of bacterial Phys. These structures have revealed how the modular architecture of these dimeric photoreceptors engages the buried chromophore through distinctive knot, hairpin, and helical spine features. When collectively viewed, these 3D structures reveal complex structural alterations whereby photoisomerization of the bilin drives nanometer-scale movements within the Phy dimer through bilin sliding, hairpin reconfiguration, and spine deformation that ultimately impinge upon the paired signal output domains. When integrated with the recently described structure of the photosensory module from Arabidopsis thaliana PhyB, new opportunities emerge for the rational redesign of plant Phys with novel photochemistries and signaling properties potentially beneficial to agriculture and their exploitation as optogenetic reagents.     

A Global Perspective of the Variables Associated with Acceptance of Evolution

The controversy of biological evolution due to conflicts with personal beliefs and worldviews is a phenomenon that spans many cultures. Acceptance of evolution is essential for global advancement in science, technology, and agriculture. Previous research has tended to focus on the factors that can influence acceptance of evolution by culture or country. Our research explored the relationship on an international scale using secondary data analysis to research evolution acceptance for 35 countries. Our results indicate significant relationships between public acceptance of evolution and religiosity, school-life expectancy, science literacy, and gross domestic product per capita. Implications and future directions for research are addressed.     

Evaluation of Gene Expression Classification Studies: Factors Associated with Classification Performance

Classification methods used in microarray studies for gene expression are diverse in the way they deal with the underlying complexity of the data, as well as in the technique used to build the classification model. The MAQC II study on cancer classification problems has found that performance was affected by factors such as the classification algorithm, cross validation method, number of genes, and gene selection method. In this paper, we study the hypothesis that the disease under study significantly determines which method is optimal, and that additionally sample size, class imbalance, type of medical question (diagnostic, prognostic or treatment response), and microarray platform are potentially influential. A systematic literature review was used to extract the information from 48 published articles on non-cancer microarray classification studies. The impact of the various factors on the reported classification accuracy was analyzed through random-intercept logistic regression. The type of medical question and method of cross validation dominated the explained variation in accuracy among studies, followed by disease category and microarray platform. In total, 42% of the between study variation was explained by all the study specific and problem specific factors that we studied together.